Is CTSS p.Arg3Trp (c.7C>T) pathogenic?

CTSS p.Arg3Trp (c.7C>T) is classified Likely benign in CTSS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-19). AlphaMissense: likely benign (0.0995); Ultra-rare (popmax 0.0165%, mid).

How common is CTSS p.Arg3Trp (c.7C>T) in the general population?

CTSS p.Arg3Trp (c.7C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CTSS p.Arg3Trp (c.7C>T)?

AlphaMissense predicts likely benign (score 0.0995) — an in-silico prediction, not a clinical call.

CTSS p.Arg3Trp

c.7C>T · rs146441878 · VCV3078793

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0995 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0995	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -5.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.79	GERP -3.7
Regional constraint	o/e 0.63	unconstrained · MANE · 32 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	14.18	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00291% 47/1,613,872 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
African / African-American	0.012%	8,333
Admixed American	0.01%	9,999
Remaining individualsnot grpmax-eligible	0.0064%	15,626
South Asian	0.00329%	30,357
European (non-Finnish)	0.00203%	49,161

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CTSS
Protein: p.Arg3Trp
Coding: c.7C>T
MANE Select: NM_004079
dbSNP: rs146441878
Type: single nucleotide variant
Location: chr1:150764757 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI 0.19 (gnomAD)
Structure: AlphaFold pLDDT 94.51 · 62 PDB

Full CTSS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTSS p.Val296= Benign ★★ same type
CTSS p.Ala243Thr Uncertain significance ★ ⚠ same type
CTSS p.Asp120Ala Uncertain significance ★ ⚠ same type
CTSS p.Asp74Asn Uncertain significance ★ ⚠ same type
CTSS p.Gly176Val Uncertain significance ★ ⚠ same type
CTSS p.His27Gln Uncertain significance ★ ⚠ same type
CTSS p.Ile193Thr Uncertain significance ★ ⚠ same type
CTSS p.Lys178Asn Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ctss-p-arg3trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown